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Biomedical subjects

H Niitani

Publications and source records attributed to H Niitani.

At least 145 records · Page 8Linked to original sources
PubMed1988

myc family gene abnormality in lung cancers and its relation to xenotransplantability.

In order to study the relationship between tumor transplantability to the nude mouse and abnormality of the myc family genes (c-myc, N-myc, L-myc) in human primary lung cancers, 32 various lung cancers were analyzed for abnormality of the myc family genes by Southern blot hybridization, and were transplanted s.c. into nude mice. Southern blot analysis showed that four non-small cell carcinomas and three small cell carcinomas had amplified c-myc and L-myc genes, respectively. Allelic deletion of the L-myc gene was observed in seven cancers, of which two also had an additional band of the c-myc gene or amplification of the L-myc gene. No abnormality of the N-myc gene was observed in this series. Of 13 cancers with abnormality of the myc family genes, 11, including all tumors with myc gene amplification, were transplantable to nude mice. Of 19 tumors without any abnormalities of the myc family genes, however, only five were transplantable to nude mice (P less than 0.005). These results indicate that abnormality of the myc family genes, especially gene amplification, might promote tumorigenic ability in xenotransplantation of lung cancers and this phenomenon might be closely related to the function of the myc gene.

Animals↗
PubMed1988

Clinical, electrophysiological, and histopathological observations in supraventricular tachycardia.

Fifty patients with supraventricular tachycardia (SVT) underwent clinical electrophysiological studies (EPS), endomyocardial biopsies and cardiac catheterizations. EPS revealed AV nodal reentrant tachycardia (AVNRT) in seven patients, AV reentrant tachycardia utilizing concealed AV bypass tracts (AVR-CBT) in nine patients, AV reentrant tachycardia utilizing AV bypass tracts with ventricular preexcitation (manifest WPW) in 13 patients, sinus nodal or intra-atrial reentrant tachycardia (SNRT or IART) in three patients, atrial flutter (AF) in nine patients, automatic atrial tachycardia (AAT) in five patients, and multifocal atrial tachycardia (MAT) in four patients. According to the clinical observations, three patients with AVNRT (43%), six with AVR-CBT (67%), six with manifest WPW (46%), two with SNRT or IART (67%), eight with AF (89%), two with AAT (40%), and two with MAT (50%) showed other accompanying clinical abnormalities. In all patients who were studied histologically, changes in the myocardium were seen; myocarditic changes, postmyocarditic changes and nonspecific abnormalities were present in six (12%), 15 (30%), and nine (18%) respectively. Myocardial changes were observed in four out of seven cases with AVNRT (57%), in six out of nine with AVR-CBT (67%), in five out of 13 with manifest WPW (38%), in two out of three with SNRT or IART (67%), in six out of nine with AF (67%), in all five cases of AAT (100%), and in two out of four with MAT (50%). Nineteen out of 32 without clinical abnormalities except for arrhythmias (59%) had myocardial changes (six had myocarditic changes, ten had postmyocarditic changes, and three had nonspecific abnormalities). On the other hand, nine out of 21 with myocarditic or postmyocarditic changes were accompanied with various arrhythmias other than SVT (two had SSS, five had AV block or rBBB, and two had VT). Elevated LVEDP was present in 36% of the group with normal myocardium and in 53% of the group with myocardial changes. However, the low EF was shown in no patients with normal myocardium but in 21% of the group with myocardial changes. The low CI was also shown in only 9% of the group with normal myocardium but in 28% of the group with myocardial changes. These results suggest that patients with SVT may exhibit several histopathological changes in the myocardium, even in the absence of any clinical organic heart disease.

Adult↗
PubMed1988

Randomized, double-blinded multicenter study. Comparison of intracoronary single-chain urokinase-type plasminogen activator, pro-urokinase (GE-0943), and intracoronary urokinase in patients with acute myocardial infarction.

Coronary recanalization rates and changes in the coagulation and fibrinolysis system were evaluated in a randomized fashion in patients with acute myocardial infarction after intracoronary administration of single-chain urokinase-type plasminogen activator (pro-urokinase: GE-0943) or urokinase. Three groups of patients were studied: group H (n = 50), 6,000 units pro-urokinase i.c.; group L (n = 44), 3,000 units pro-urokinase i.c.; and group U (n = 54), 960,000 IU urokinase i.c. Coronary recanalization rates determined angiographically after 45 minutes of intracoronary infusion averaged 90% in group H, 59% in group L, and 61% in group U. The differences were statistically significant between group H and the latter two groups. Pro-urokinase affected plasma proteins of the fibrinolytic system to a lesser degree than urokinase. Bleeding complications were present in one patient in group L, in none in group H, and in five in group U. Thus, intracoronary administration of 6,000 units pro-urokinase is more effective in coronary thrombolysis and causes less systemic fibrinogenolysis than intracoronary administration of urokinase.

Adult↗
PubMed1988

Restorative activity of muroctasin on leukopenia associated with anticancer treatment.

The restorative effect of N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin), a muramyl dipeptide derivative, was studied in patients with leukopenia associated with anticancer chemotherapy and radiation therapy. The drug was subcutaneously administered to 102 cancer patients in a single doses of 200 or 400 micrograms, and each dosage was given either every day for 6 days or every other day over a 5-day period. White blood cell (WBC) counts were made before, during and after treatment. MDP-Lys(L18) was most effective in patients receiving the drug every day and the 400 micrograms dose was somewhat superior to the 200 micrograms dose in augmenting the WBC population. Overall, the response to MDP-Lys(L18), in terms of the increase in number of WBCs, was good to excellent in 41.6% of patients. MDP-Lys(L18) was considerably more effective in patients with solid tumors than in those with hematological malignancies. The most common side effect was fever, which was dose-dependent, more pronounced with alternate-day dosing, and generally well controlled with antipyretics. The results of this study indicate that MDP-Lys(L18) is useful in improving the WBC count in leukopenic cancer patients treated with anticancer therapy. Considering the efficacy and side effect profiles together, it is suggested that 200 micrograms/day for 6 consecutive days is the optimal treatment regimen.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

[Effects of bathing on cardiac function in patients with myocardial infarction: hemodynamic and Doppler echocardiographic studies].

Hemodynamic changes during bathing in patients with myocardial infarction were studied using a Swan-Ganz catheter and Doppler echocardiography. The subjects consisted of 14 patients with myocardial infarction (mean age 55.6 years), including the six extensive ones of the anterior wall, five of the anteroseptal wall, two of the inferior wall, and one of the inferoposterior wall. Bathing was by means of 42 degrees C tap water for five min in the supine position in a Hubbard tank. Pulsed wave Doppler was used to analyze left and right ventricular inflow velocity patterns, and continuous wave Doppler was employed to measure right ventricular outflow velocity. Blood pressure, pulmonary arterial pressure, pulmonary arterial wedge pressure and right atrial pressure increased significantly during bathing. After bathing, these parameters decreased and remained lower than the baseline levels before bathing. Heart rate and the cardiac index increased significantly during bathing, but decreased after bathing. The systemic vascular resistance index and pulmonary vascular resistance index decreased significantly during bathing, but increased after bathing. The A/R ratio at the left and right ventricular inflow tracts increased during bathing, and right ventricular outflow velocity increased significantly. However, when the subjects were categorized into two groups, i.e., those whose pulmonary arterial pressure consistently increased to the higher level than the average during bathing and those who did not show any increase, the A/R ratio at the inflow tract of the left ventricle increased significantly during bathing in the former group, but there was no significant change in the latter group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

[Hyperthyroidism due to a TSH-secreting pituitary tumor].

A 28-year-old female with a 12-year history of goiter is presented. She had both clinical and laboratory evidence of hyperthyroidism, and her serum TSH was persistently and markedly elevated after treatment with antithyroid drugs. A TRH stimulation test resulted in no further rise in serum TSH after cessation of medication. Menses were regular and serum prolactin levels were normal. Serum LH and FSH responses to LHRH stimulation test were normal. No other evidence of pituitary or peripheral endocrine deficiencies existed. She underwent a subtotal thyroidectomy followed by 131I therapy three years later. A pituitary adenoma with sphenoidal and suprasellar extension was completely removed by transphenoidal approach. On light microscopy, it was mostly composed of chromophobic cells with occasional calcification showing sinusoidal pattern. On electron microscopy, most of the cells contained fine granules, which suggested thyrotroph. The immunoperoxidase technique revealed TSH beta in the cytoplasm of some adenoma cells. Three days postoperatively the patient's serum TSH levels returned to normal. TRH stimulation test produced a normal response in serum TSH. The patient was diagnosed hypothyroid by laboratory findings and is currently on thyroid replacement therapy. The patient became pregnant and delivered twice prior to the operation for pituitary adenoma. The previously reported TSH secreting adenomas associated with hyperthyroidism were reviewed.

Adenoma↗
PubMed1987

Alterations in fine structures of myofibrils and structural proteins in patients with dilated cardiomyopathy--studies with biopsied heart tissues.

Ultrastructural and biochemical alterations in myofibrils (Mf) were studied in biopsied myocardial tissues in 11 patients with dilated cardiomyopathy (DCM) and compared with those in non-hypertrophic control and secondary hypertrophic (SHT) heart muscles. Transverse diameters of biopsied cardiac myocytes increased significantly in both of SHT and DCM, and ultrastructural changes were similar in quality in both of them. Volume densities of Mf were 61.1 and 59.9% on average in control and SHT myocardial cells, respectively, and they were not significantly different. But in DCM volume density was significantly less (49.8% in left ventricular myocytes), and inverse relation between that and diameter of cardiac myocytes was observed (p less than 0.01). Electrophoretic pattern and relative composition of major structural proteins from control and SHT heart muscles were similar and statistically insignificant. In DCM, relative contents of myosin heavy chain and alpha-actinin decreased significantly and distinctively in all of cases suggesting primary degradation of myofibrils.

Biopsy↗
PubMed1987

[Bleomycin].

Bleomycin, with was discovered by H. Umezawa et al., is being used throughout the world of its clinically proved effect on tumors such as squamous epithelical carcinoma, malignant lymphoma etc. Elucidation on the mechanism of its effect has advanced to a molecular level, and it is believed that the agent cuts a DNA chain via a ferrum chelate [active type of BLM-Fe(III) chelate]. The heterologous dosage forms (oleosu, ointment) were developed for exerting a long-lasting at local tumor sites. And moreover, the assessment of derivatives to obtain increase the antitumor effect and reduce side effects provided clues leading to the development of Peplomycin. The essential clinical applications of this agent involve its combined with other carcinostatics and combination therapy with surgery and radiation. Many regimens have been studied in order to increase its anti-tumor effect in each field of application. There is the characteristic feature of side effects on bleomycin, which has no myelotoxicity but has fibroid lung as dose limiting toxicity. So it is necessary for the agent to be used carefully in order to reduce this pulmonary toxicity. Selection of cases, method of administration, method of early diagnosis and treatment of side effects should also be taken into consideration.

Bleomycin↗
PubMed1987

[Randomized comparison of continuous and intermittent oral administration of 5'-deoxy-5-fluorouridine in the treatment of advanced gastric cancer; a phase II trial by the Multi-institutional Cooperative Study Group].

To investigate the optimal dosage schedule for 5'-deoxy-5-fluorouridine (5'-DFUR), a randomized comparative study was performed in patients with inoperable or advanced gastric cancer. Eight hundred mg/m2/day of 5'-DFUR was administered in the continuous administration group, while in the intermittent administration group 1,400 mg/m2/day was given for 4 days followed by 3 days with no medication in a one-week cycle, making the total dose 5,600 mg/m2/week in both regimens. In both groups, 5'-DFUR was administered for more than 4 weeks. Overall response rate was 14.3% (3/21) for both administration methods. The response rate for the primary site was 9.5% (2/21) in the continuous administration group, and 14.3% (3/21) in the intermittent group. As to toxicity, the incidence of diarrhea was 26.7% in the continuous group and 4.2% in the intermittent group. Although there was no significant difference between these two dosage schedules in efficacy and toxicity, the lower incidence of diarrhea suggested the clinical usefulness of the intermittent administration method. This result emphasized the need to further studies to investigate the most appropriate dosage schedule for fluorinated pyrimidine derivatives.

Administration, Oral↗
PubMed1987

[Analysis of drug sensitivity by successive colony-forming assay].

It is difficult to predict the adequate doses of effective drugs which must be administered in cancer chemotherapy. We have developed a successive colony-forming assay in order to analyze changes of drug sensitivity in human cancer cell lines, and it is used as a model of cancer chemotherapy. Presently, widely used methods include the clonog ceni assay as in vitro sensitivity test established by Salmon and Hamberger et al., for revealing effective drugs. However, formation of a second colony using initial colony-forming cells has not yet been performed. We therefore analyzed the changes occurring in drug sensitivity in 2nd and 3rd colony-forming assays. Using a human lung adenocarcinoma cell line PC-9 (established by Hayata at the Surgical Department in Tokyo Medical School), we measured the changes in sensitivity to CDDP and its derivatives. After picking up the colony-forming cells by micropipette and culturing them in culture medium, we tried to incubate them for 1 hour with the anticancer drug, and then replate them in soft agar. This technique is called "2nd colony-forming assay". We were able to carry this out three times. The results obtained showed that the anti-tumor effect of 254S was the same as that of CDDP, whereas that of CBDCA was less than either of them. Although these tendencies were noticeable even in the 2nd colony-forming assay, the sensitivities to CDDP and its derivatives were diminished in the 3rd colony-forming assay.

Adenocarcinoma↗
PubMed1987

[Serum NSE (neuron-specific enolase) levels in small cell lung cancer, with special reference to the measurement of serial serum NSE levels].

Serum neuron-specific enolase (NSE) was measured in 105 patients with lung cancer without prior therapy. Increasing serum levels of NSE were observed in 84% of cases of small cell lung cancer (SCLC). 11% of adenocarcinomas, 18.5% of squamous cell carcinomas and 37.5% of large cell carcinomas. Serum NSE levels changed in parallel with the effect of initial treatment. Although two of 5 patients with SCLC, in whom serial NSE levels were measured after treatment, showed elevation of serum NSE levels before clinical relapse, elevated serum NSE levels were not observed in 3 patients at clinical relapse. These data seem to suggest that measurement of serial NSE is useful for predicting relapse prior to clinical recognition. However, it still remains an important point to carry out clinical general surveillance for relapse.

Adult↗
PubMed1987

[FO-152].

5'-O-(L-valyl)-5-fluorouridine hydrochloride (FO-152) is a derivative of 5-fluorouridine. In preclinical studies, FO-152 has demonstrated more favorable antitumor effect with greater therapeutic index compared with the parent compound, 5-fluorouridine. A phase I study was performed in 38 cases with advanced cancer. Myelosuppression was dose limiting, with leukopenia more pronounced than thrombocytopenia. Other side effects included mild hot feeling of the body during infusion and slight G.I. toxicities. Clinical responses were seen in patients with adenocarcinoma of the stomach, lung, etc. FO-152 has major advantages over 5-fluorouridine in terms of reduced toxicity. The recommended phase II dose for patients with solid tumors is 250 mg/m2 X 1, or 35 mg/m2 X 5 consecutive days with a 4-week rest, provided there is reversal of drug related myelosuppression.

Absorption↗
PubMed1987

[Phase I study of natural interferon-gamma].

We report a clinical study of toxicity and pharmacokinetics of intravenously administered natural interferon-gamma. Twenty three cases with metastatic cancer were given interferon-gamma at doses of 10 X 10(4)-400 X 10(4) IU in single injection. Another twenty three cases were administered at doses of 5 X 10(4)-50 X 10(4) IU/day every day for thirty days. Side effects associated with natural interferon-gamma administration were qualitatively similar to those previously reported for alpha, and beta interferon treatment. After intravenous injection, interferon-gamma was cleared monoexponentially with a short half-life of 120 minutes from the circulation. One case with disseminated thyroid cancer showed minor response.

Drug Evaluation↗
PubMed1987

[Role of natural killer cells in the antimetastatic effect of defibrinogenation with batroxobin].

The antimetastatic effects of defibrinogenation with batroxobin were investigated in normal mice and in mice with depressed or activated natural killer (NK) cell activity. Batroxobin inhibited the formation of lung metastases after intravenous inoculation of the F10 subline of B16 melanoma. Inhibition of NK activity by treatment of mice with anti-asialo GM1 antibody abrogated the antimetastatic effects of Batroxobin. Conversely, augmentation of NK cell activity by poly I:C plus treatment with batroxobin produced additive antimetastatic effects. Studies on the mechanism of interaction between Batroxobin and NK cells revealed that Batroxobin treatment did not affect splenic NK activity in vitro. From these data, it was found that the antimetastatic effects of batroxobin are dependent on the level of NK activity in the host.

Animals↗
PubMed1987

[Clinical investigation of carbohydrate antigen CA-50].

The CA-50 enzyme immunoassay kit (EIA kit) that has been developed with the use of C-50 monoclonal antibody prepared by L. Lindholm et al. was evaluated for diagnosis of human cancer. The levels of CA-50 in the sera were determined using this kit supplied from Mitsui Pharmaceuticals, Inc. Co. in 759 healthy donors, 728 patients with benign disease and 1,263 untreated patients with cancer. A CA-50 concentration of 40 U/ml of serum was used as the cut-off value. Patients with pancreatic cancer and patients with bile duct cancer had high positive incidence of 75% and 68%, respectively, compared with a low positive incidence of under 40% in patients with other cancers. On the other hand, positive rates in patients with benign disease were as low as 13%. Comparison of the serum levels of CA-50 with CA19-9 in the same samples did not exhibit complete positive correlation in patients with pancreatic cancer, patients with bile duct cancer and patients with liver cancer. These findings indicated that C-50 antibody reacted with two epitopes of CA19-9 and sialosyllactotetraose. From the above results, the usefulness of CA-50 as a tumor marker for pancreatic cancer and bile duct cancer was recognized with this EIA kit.

Adult↗